Dominant and cryptic antigens in the MHC class I restricted T cell response across a complex minor histocompatibility...

T cell responses against complex antigens are often directed against a limited set of immunodominant determinants. We have studied this phenomenon at the level of cellularly processed peptides recognized by CTL in the B6 anti-BALB.B minor histocompatibility (H) barrier, comprising at least 29 antigen loci. B6 anti-BALB.B CTL always recognized three reverse phase HPLC fractions in BALB.B eluates, whether the latter were obtained from cell lysates or immunoaffinity purified class I molecules. One of these immunodominant epitopes (termed IDE-1) was H-2Db restricted, and two (termed IDE-2 and IDE-3) were H-2Kb restricted. B6 mice were immunized with spleen cells from B6 congenic mice carrying single minor H loci from BALB.B with the aim to assign IDE to given minor H loci and to investigate whether additional epitopes could be identified in the absence of the immunodominant ones. IDE-3 was found to be associated to the locus H-28; in addition five so called cryptic epitopes were defined. Induction of CTL against these epitopes required immunization with cells of the congenic strain; BALB.B spleen cells failed to immunize. One subgroup of these epitopes (those associated to H-8, H-19 and H-25) were nevertheless found to be processed and loaded in class I molecules of BALB.B cells, while there was no evidence for this for H-35 and H-36. For 10 additional congenic strains, no CTL response was detected. The results are discussed in relation to the genetic and molecular basis of minor H antigens, and mechanisms for epitope dominance operating at the level of the APC or responding T cells.